This is a proposal to investigate incorporation of 2-thiouracil into the melanin structure of hamster melanoma cells using Fortner transplantable hamster melanomas, the RPMI 3460 established melanoma cell line, and dimethylbenzanthracene-induced melanomas of hamster skin. The project is designed to evaluate the potential of using this drug as a basis for selective chemotherapeutic methods to destroy malignant melanotic melanomas. The study is intended to provide a more detailed understanding of how thiouracil becomes incorporated into melanin structure, and what possible structural modifications of the melanin polymer it might cause. Various thiouracil derivatives will be examined for their ability to form "pheomelanins" in order to learn what general characteristics of the molecule are necessary for its uptake and utilization in pheomelanin synthesis. Cytotoxicity and radiotoxicity of thiouracil will be studied in the cell culture model system as well as in tumor-bearing hamsters, and attempts will be made to obtain amplification of the effects of other anti-tumor drugs. If possible, the animals will be immunized against thiouracil pheomelanoproteins, and attempts made to cause immunological rejection of melanomas by animals treated with thiouracil. BIBLIOGRAPHIC REFERENCE: Steinberg, M. L. and Whittaker, J. R. 1976. Stimulation of melanotic expression in a melanoma cell line by theophylline. J. Cell. Physiol. 87:265-276.